Is FUT4 p.Pro83Arg (c.248C>G) pathogenic?

FUT4 p.Pro83Arg (c.248C>G) is classified Uncertain significance in FUT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.0948); Very rare (popmax 0.000434%, nfe).

How common is FUT4 p.Pro83Arg (c.248C>G) in the general population?

FUT4 p.Pro83Arg (c.248C>G) is very rare (popmax 0.000434%, nfe) (gnomAD).

What do computational predictors say about FUT4 p.Pro83Arg (c.248C>G)?

AlphaMissense predicts likely benign (score 0.0948) — an in-silico prediction, not a clinical call.

FUT4 p.Pro83Arg

c.248C>G · VCV4027306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0948 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000434%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0948	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP -1.5, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 666 bp · p 5.4e-09 · regional, not allelic
Overall
CADD	19.25	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000434% European (non-Finnish) · 5/1,152,084 alleles

Filtering AF 0.000127% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000324% 5/1,541,656 alleles · very rare exomes 5/1,389,402 · genomes 0/152,254 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FUT4
Protein: p.Pro83Arg
Coding: c.248C>G
MANE Select: NM_002033
Type: single nucleotide variant
Location: chr11:94544381 (GRCh38)
Gene constraint: LOEUF 1.216 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 74.21
Residue 83: the 'disordered' region

Full FUT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FUT4 p.Asp516Glu Likely benign ★★ same type
FUT4 p.Pro54= Benign ★★ same type
FUT4 p.Ala119Thr Uncertain significance ★ ⚠ same type
FUT4 p.Ala120Gly Uncertain significance ★ ⚠ same type
FUT4 p.Ala128Val Uncertain significance ★ ⚠ same type
FUT4 p.Ala14Gly Uncertain significance ★ ⚠ same type
FUT4 p.Ala14Ser Uncertain significance ★ ⚠ same type
FUT4 p.Ala157Pro Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fut4-p-pro83arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown